Electrophilic Aromatic Trifluoromethylthiolation with the Second Generation of Trifluoromethanesulfenamide

Abstract

Direct trifluoromethylthiolation of various aromatic and heteroaromatic compounds, variously substituted, can be performed with the second generation of trifluoromethanesulfenamide via a ‘Friedel–Crafts-like reaction’. This reaction requires mild conditions with a catalytic amount of protic or Lewis acid. Good results have been obtained, even with aromatic compounds bearing deactivating substituents.

Key words

trifluoromethylthiolation - fluorine - arenes - heterocycles - trifluoromethanesulfenamide

• References and Notes

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• 13 Typical Procedure: A 10 mL sealed tube equipped with a magnetic stirrer was charged with the arene (0.50 mmol, 1.0 equiv) and TsNMeSCF₃ (1a) or TsNMeSCF₂CF₃ (1b; 1.2 equiv) in anhyd DCE. The reaction was stirred at r.t. for 1 min and triflic acid was added slowly (0.2 equiv) and the reaction was stirred at 80 °C for 18 h. The progress of the reaction was checked by ¹⁹F NMR with PhOCF₃ as internal standard. After completion, the reaction was warmed to r.t. and the solvent was removed under vacuum and the residue was purified by flash chromatography to give the desired product.
• 14 4-[(Trifluoromethyl)sulfanyl]benzene-1,3-diol (3b): brown solid; mp <50 °C. ¹H NMR: δ = 7.41 (d, ³ J _H,_H = 8.6 Hz, 1 H), 6.56 (d, ³ J _H,_H = 2.7 Hz, 1 H), 6.85 (dd, ³ J _H,_H = 8.6, 2.7 Hz, 1 H), 4.50–6.10 (br, 2 H). ¹³C NMR: δ = 161.1, 159.5, 139.6, 128.8 (q, ¹ J _C,_F = 315 Hz), 109.9, 103.0, 99.62 (q, ³ J _C,_F = 1.7 Hz). ¹⁹F NMR: δ = –44.52 (s, 3 F). Anal. Calcd for C₇H₅F₃O₂S: C, 40.00; H, 2.40; S, 15.26. Found: C, 40.12; H, 2.29; S, 15.47.
• 15 Synthesis of 2,4-Dimethoxy-1-[(pentafluoroethyl)sulfanyl]benzene (4a): ¹H NMR: δ = 7.51 (d, ³ J _H,_H = 8.5 Hz, 1 H), 6.50–6.52 (m, 2 H), 3.87 (s, 3 H), 3.83 (s, 3 H). ¹³C{¹⁹F} NMR: δ = 164.3, 162.7, 141.0, 120.0 (CF₂), 118.9 (CF₃), 105.7, 101.7 (t, ³ J _C,_F = 2 Hz), 99.3, 56.1, 55.62. ¹⁹F NMR: δ = –82.94 (t, ³ J _F,_F = 3.4 Hz, 3 F), –93.06 (q, ³ J _F,_F = 3.5 Hz, 2 F). Anal. Calcd for C₁₀H₉F₅O₂S: C, 41.67; H, 3.15; S, 11.12. Found: C, 41.79; H, 2.91; S, 11.4.